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Modulation of neuronal CXCR4 by the μ-opioid agonist DAMGO

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Abstract

The chemokine receptor CXCR4 regulates neuronal survival and differentiation and is involved in a number of pathologies, including cancer and human immunodeficiency virus (HIV). Recent data suggest that chemokines act in concert with neurotransmitters and neuropeptides, such as opioids. This study aimed to determine whether μ-opioid agonists alter the effect of CXCL12 (the specific CXCR4 ligand) on central neurons. Neuronal expression of CXCR4 and μ-opioid receptors (MORs) was analyzed by Western blot, immunostaining, and flow cytometry. Single-cell studies showed that all CXCR4-positive neurons coexpress MORs. Treatment of neuronal cultures with the selective MOR agonist DAMGO or the endogenous peptide endomorphin-1 inhibited intracellular signaling pathways (ERK1/2 and Akt) activated by CXCL12. Furthermore, DAMGO abolished the neuroprotective effect of CXCL12 in N-methyl-d-aspartate (NMDA) neurotoxicity studies. The effects of DAMGO and endomorphin-1 were inhibited by a general or a μ-specific opioid receptor antagonist, and not caused by changes in neuronal CXCR4 levels. DAMGO did not affect CXCL12-induced internalization of CXCR4. The authors propose that interactions between MOR and CXCR4 signaling can modulate the action of CXCL12 on neuronal survival—which may have important implications to neuroAIDS as well as other neuroinflammatory disorders.

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Authors and Affiliations

  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, NCB Room 8804, 19102, Philadelphia, PA, USA

    Jeegar P. Patel, Rajarshi Sengupta, Giuseppe Bardi, Muhammad Z. Khan, Anna Mullen-Przeworski & Olimpia Meucci

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  1. Jeegar P. Patel
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  2. Rajarshi Sengupta
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  3. Giuseppe Bardi
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  4. Muhammad Z. Khan
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  5. Anna Mullen-Przeworski
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  6. Olimpia Meucci
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Correspondence to Olimpia Meucci.

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Patel, J.P., Sengupta, R., Bardi, G. et al. Modulation of neuronal CXCR4 by the μ-opioid agonist DAMGO. Journal of NeuroVirology 12, 492–500 (2006). https://doi.org/10.1080/13550280601064798

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  • DOI: https://doi.org/10.1080/13550280601064798

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